Immunoglobulin Deficiency as an Indicator of Disease Severity in Patients with COVID-19

Faeq Husain-Syed, István Vadász, Jochen Wilhelm, Hans-Dieter Walmrath, Werner Seeger, Horst-Walter Birk, Birgit Jennert, Hartmut Dietrich, Susanne Herold, Janina Trauth, Khodr Tello, Michael Sander, Rory E Morty, Heiko Slanina, Christian G Schüttler, John Ziebuhr, Shadi Kassoumeh, Claudio Ronco, Fiorenza Ferrari, Klaus Warnatz, Klaus Stahl, Benjamin Seeliger, Marius M Hoeper, Tobias Welte, Sascha David
American Journal of Physiology. Lung Cellular and Molecular Physiology 2020 November 25
Despite the pandemic status of COVID-19, there is limited information about host risk factors and treatment beyond supportive care. Immunoglobulin G (IgG) could be a potential treatment target. Our aim was to determine the incidence of IgG deficiency and associated risk factors in a cohort of 62 critical ill COVID-19 patients admitted to two German ICUs (72.6% male, median age: 61 years). 13 (21.0%) of the patients displayed IgG deficiency (IgG <7 g/L) at baseline (predominant for the IgG1, IgG2, and IgG4 subclasses). IgG-deficient patients had worse measures of clinical disease severity than those with normal IgG levels (shorter duration from disease onset to ICU admission, lower ratio of PaO2 to FiO2 , higher Sequential Organ Failure Assessment score, and higher levels of ferritin, neutrophil-to-lymphocyte ratio and serum creatinine). IgG-deficient patients were also more likely to have sustained lower levels of lymphocyte counts and higher levels of ferritin throughout the hospital stay. Furthermore, IgG-deficient patients compared to those with normal IgG levels displayed higher rates of acute kidney injury (76.9% vs. 26.5%; p=0.005) and death (46.2% vs. 14.3%; p=0.012), longer ICU (28 [6-48] vs. 12 [3-18] days; p=0.012) and hospital length of stay (30 [22-50] vs. 18 [9-24] days; p=0.004). Multivariable logistic regression showed increasing odds of 90-day overall mortality associated with IgG-deficiency (OR 12.8, 95% CI 1.5-108.4; p=0.019). IgG deficiency might be common in critically ill COVID-19 patients, and warrants investigation as both a marker of disease severity as well as a potential therapeutic target.

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